These costs amount to approximately 5.7% of the entire US health expenditure. The cost of lost productivity due to obesity amounts to approximately $3.9 billion, while another $33 billion is spent annually on various weight loss products and services.
Other indices used to estimate the degree and distribution of obesity include the 4 standard skin thicknesses (ie, subscapular, triceps, biceps, suprailiac) and various anthropometric measures, of which waist and hip circumferences are the most important.
Two major groups of factors with a balance that variably intertwines in the development of obesity are genetics, which is presumed to explain 40-70% of the variability in obesity variance, and environmental factors .
The high prevalence of obesity in the children of parents who are obese and the high concordance of obesity in identical twins suggest a significant genetic component to the pathogenesis of obesity, the secular trends of the last few decades, which are coincident with recent changes in dietary habits and activity, also suggest a significant role for environmental factors.
The major role of leptin in body weight regulation is to signal satiety to the hypothalamus and, thus, reduce dietary intake and fat storage while modulating energy expenditure and carbohydrate metabolism to prevent further weight gain .
Unfortunately, unlike the Ob/Ob mouse model in which this peptide was first characterized, most humans who are obese are not leptin-deficient but rather leptin-resistant and, thus, have elevated circulating leptin levels.
While most human obesity is polygenic (>90% of cases), the recognition of monogenic variants has greatly enhanced our knowledge about the etiopathogenesis of obesity.
Monogenic models for obesity in humans and experimental animals
The various available monogenic models have greatly increased our knowledge about mechanisms for the development of obesity, and they also have provided multiple potential targets for future antiobesity medications.
Of particular interest is the fact that patients with POMC mutations, because of the deficiency in MSH production that results, tend to have red-colored hair. Also, because of their diminished adrenocorticotropic hormone (ACTH) levels, they tend to have central adrenal insufficiency.
Some recent data suggest that as many as 5% of children who are obese have MC4 or POMC mutations. If confirmed, these would be the most common identifiable genetic defects associated with obesity in humans (band 2p23 for POMC and band 18q21.3 for MC4 ).
The Db/Db mice have mutations of the leptin receptor in the hypothalamus.
Fa/Fa mice also have leptin-receptor mutations.
These mice have early-onset obesity and hyperphagia like the Ob/Ob mice, but they also have normal or elevated leptin levels.
Human counterparts of this model are very rare and are associated with hyperphagia, hypogonadotrophic hypogonadism, and defective thyrotropin secretion, but they are not associated with hypercortisolism, hyperglycemia, and hypothermia as occurs in Db/Db mice (band 1p31).
In addition to the above monogenic models of obesity, genome-wide linkage analyses and microarray technology have revealed a rapidly growing list of potential susceptibility obesity genes. Among those identified that are being actively studied are genes on chromosome arms 2p, 10p, 5p, 11q, and 20q.
In the same line as the evidence that proved Helicobacter pylori as the cause for peptic ulcer disease, some evolving data suggest that a significant inflammatory and possibly infective etiology may exist for obesity. Adipose tissue is known to be a repository of various cytokines, especially interleukin-6 and tumor necrosis factor-alpha
Internationally: The prevalence of obesity worldwide is increasing, and this is particularly occurring in the developed nations of the Northern Hemisphere, including the United States, Canada, and most of Europe.
Available data from the MONICA (monitoring cardiovascular) disease study in Europe suggest that at least 15% of men and 22% of women in Europe are obese.
Similar data now are being reported from many developing countries, particularly in Asia and, to a lesser extent, in Africa.
Reports from countries such as Malaysia, Japan, Australia, New Zealand, and China detail an epidemic of obesity in the last 2-3 decades.
Data from the Middle Eastern countries of Bahrain, Saudi Arabia, Egypt, Jordan, Tunisia, and Lebanon, among others, exhibit this same disturbing trend, with alarming levels of obesity often exceeding 40%, particularly worse in women.
Data from the Caribbean and South America also highlight similar trends. While data from Africa on this issue are scant, a clear and distinct secular trend of profoundly increased BMIs clearly exists when people from Africa immigrate to northwestern hemispheric countries. Studies comparing these indices among Nigerians residing in Nigeria and recent immigrants to the United States show this trend very poignantly.
Data available from insurance company databases and large prospective cohorts such as the Framingham and NHANES studies clearly indicate that obesity is associated with a significant increase in both morbidity and mortality.
The degree of obesity (generally indicated by the BMI) at which a discernible increase in mortality occurs is, however, higher for African Americans and Hispanic Americans than for white Americans, suggesting a significant racial spectrum and difference in this effect.
Obesity is a cosmopolitan disease that affects all races worldwide.
However, certain ethnic and racial groups appear to be particularly predisposed.
Pima Indians of Arizona and other ethnic groups native to North America have a particularly high prevalence of obesity.
Polynesians, Micronesians, Anurans, Maoris of the West and East Indies, African Americans in North America, and the Hispanic populations (both Mexican and Puerto Rican in origin) in North America also have particularly high predispositions to developing obesity.
Secular trend studies clearly underline the marked importance of environmental factors (particularly dietary issues) in the development of obesity. Many of the genetically similar cohorts of the above named high-risk ethnic and racial groups have far less prevalence for obesity in their countries of origin, but this changes significantly when such groups have immigrated to the affluent Northern Hemisphere, with altered dietary and activity habits. These findings form the core concept of the thrifty gene hypothesis espoused by Neal et al.
Clearly evidenced in secular trends, children (particularly adolescents) who are obese have a very high probability of growing to be adults who are obese; hence, this bimodal distribution of obesity portends a large-scale obesity epidemic in the next few decades.
A full history must include a dietary inventory and an analysis of the subject's activity level.
Screening questions to exclude depression are vital because this may be a consequence or a cause of excessive dietary intake and reduced activity.
Because almost 30% of patients who are obese have eating disorders, screen for this in the history. The possibility of binging, purging, lack of satiety, food-seeking behavior, and other abnormal feeding habits need to be identified because management of these habits is crucial to the success of any weight management program.
Also, investigate whether any of the previously mentioned comorbidities have occurred, and include questions to exclude the possible rare causes of secondary obesity
When asking patients about their history, investigate whether the rest of the patient's family also has weight problems, inquire about the expectations of the subject, and estimate the level of motivation of the subject.
Comorbidities related to obesity include the following
Cardiovascular - Essential hypertension, coronary artery disease, left ventricular hypertrophy, cor pulmonale, obesity-associated cardiomyopathy, accelerated atherosclerosis, pulmonary hypertension of obesity
Central nervous system - Stroke, idiopathic intracranial hypertension, meralgia, paresthetica
Metabolic - Insulin resistance, hyperinsulinemia, type 2 diabetes mellitus, dyslipidemia (characterized by high total cholesterol, high triglycerides, normal or elevated low-density lipoprotein, and low high-density lipoprotein)
Reproductive - Anovulation, early puberty, infertility, hyperandrogenism and polycystic ovaries in women, hypogonadotrophic hypogonadism in men
Obstetric and perinatal - Pregnancy-related hypertension, fetal macrosomia, pelvic dystocia
In the clinical examination, include measurement of the anthropometric parameters and the standard detailed examination required for the evaluation of persons with any chronic multisystemic disorder such as obesity.
Hepatic panel: This is expected to be normal but may be abnormal (elevated transaminases in the setting of NASH).
Thyroid function tests
These typically are normal but checking them in order to detect cases of primary hypothyroidism (characterized by increased serum thyrotropin and normal or reduced levothyroxine and/or triiodothyronine levels) is worthwhile.
Among the various procedures relevant to the management of patients who are obese are procedures to estimate the degree of visceral and subcutaneous fat. These include the standard anthropometric measurements and caliper-derived skin thickness estimates.
Histologic Findings: Hypertrophic obesity characterized by enlarged fat cells is typical of android abdominal obesity. Hypercellular obesity, on the other hand, is more variable, and it is typical of obesity with an onset in childhood or adolescence but invariably also is found in subjects with severe obesity.
Medical Care: While obesity in itself is associated with increased morbidity and mortality, massive poorly monitored weight loss and/or weight cycling can have equally dire consequences. Among the important potential complications to watch out for in the setting of weight loss are cardiac arrhythmias; electrolyte derangements, of which hypokalemia is the most important; hyperuricemia; and psychologic sequelae, including depression and the development of eating disorders (particularly binge-eating disorders).